低氧性肺动脉高压大鼠肺内FHL1的表达

Expression of FHL1 in the lung of rats with hypoxic pulmonary hypertention

目的了解低氧肺动脉高压时肺内FHL1与肺血管重建的关系。方法将20只雄性Wistar大鼠分为对照组和低氧肺动脉高压组,低氧肺动脉高压组以常压低氧复制大鼠肺动脉高压模型,以微导管法测定各组大鼠肺动脉压,采用免疫组织化学法检测各组大鼠肺内FHL1、细胞骨架蛋白1(Talin1)及细胞周期素D(Cyclin D)的表达,对肺组织切片进行图像分析。结果低氧3周后,低氧肺动脉高压组大鼠形成明显的肺动脉高压,管壁增厚,管腔狭窄,大鼠肺动脉压(2.86±0.39)kPa,右心室肥厚指数[RV/(LV+S)]为(43.53±3.38)%,管壁厚度占外径的百分比(WT%)为(35.24±11.2)%,管壁面积占血管总面积的百分比(WA%)为(55.09±12.38)%,分别与对照组[(1.35±0.28)kPa、(23.68±3.48)%、(23.63±9.74)%和(41.62±12.83)%]相比升高(P<0.01);肺小动脉FHL1免疫阳性染色在低氧肺动脉高压组大鼠为1.48±0.03,与对照组(0.86±0.02)相比增强(P<0.01);低氧肺动脉高压组大鼠Talin1免疫阳性染色为(1.52±0.04),与对照组(0.92±0.03)相比增强(P<0.01);低氧肺动脉高压组大鼠Cyclin D免疫阳性染色为(1.46±0.02),与对照组(0.73±0.04)相比增强(P<0.01)。结论低氧所致FHL1的合成增多在低氧性肺血管重建和肺动脉高压的发病过程中起一定的作用,其作用可能与Talin1、Cyclin D有关。

[ Objective] To test the role of FHL1 in the development of hypoxic pulmonary hypertension. [Methods] Twenty male Wistar rats were divided into two groups and exposed to air and isobaric hypoxia for 3 weeks, respectively. The pulmonary artery pressure was measured by right cardiac catheterization. The ex- pression of FHLI, Talinl and Cyclin D in the lungs of rats was measured by immunohistochemical staining. The histological sections of the lungs were examined using a computerized image analyzer. [Results] The pulmonary artery pressure in the exposed rats increased. The chronic hypoxia also elicited the thickening of the wall and the narrowin~ of the lumen of Dulmonarv arterioles.It led to the increases of the pulmonary artery pressure, the index of right ventricular hypertrophy [RV/ （LV ＋ S）], the ratio of vascular wall thickness/ vascular external diameter （WA%） and the ratio of vascular wall area/total vascular area （WT%） compared to the controls （PAP 2.86 ±0.39 kPa vs 1.35 ± 0.28 kPa; [RV / （LV ＋ S）： 43.53 ± 3.38 vs 23.68 ± 3.48; WT%： 35.24± 11.2 vs 23.63 ±9.74; WA%： 55.09±12.38 vs 41.62± 12.83] respectively, P〈0.05）. The positive staining of FHL1, Talinl and Cyclin D in the wall of pulmonary arteriole of the exposed rats were significantly stronger than those of controls （P〈O.O1）. [Conclusion] The FHLI may play an important role in the patho genesis process of hypoxic pulmonary vascular remodeling and pulmonary hypertension, and the possible molecule mechanism of it＇s relationship between Talinl and Cyclin D.